Previous experiments under this grant have shown that after several days of treatment of the eye with a cholinesterase inhibitor (echothiophate iodide or DFP), the pupil which after the first treatment constricts maximally, redilates. This development of apparent subsensitivity to the anti-ChE drug is also associated with a development of complete insensitivity to the miotic effects of carbachol or pilocarpine. This phenomena requires the presence of cholinergic nerves or exogenous ACh. Further experiments showed that the sensitivity of the cat eye to the miotic effects of pilocarpine or carbachol can also be affected by exposure of the animals to environmental lighting of greater than normal intensity and duration (over stimulation) or the sensitivity of the iris to these drugs can be increased by keeping the animals in complete darkness for a few days (stimulus deprivation). We are planning to investigate the possibility that prostaglandins may play a role in these alterations in cholinergic drug sensitivity. In connection with these planned investigations we are currently studying the mechanism of entry of PGs into the eye and the mechanism of their removal and/or inactivation. Experiments up to date indicate that prostaglandins are removed from the mammalian eye by a saturable transport process located at the ciliary process. The mechanism of this apparent prostaglandin transport process and some possible inhibitors of this carrier-mediated transport will be studied in greater detail during the year.